The research is at present focused on the following areas: (1) the relative roles of metabolic activation and detoxification in determining both mutagenic and carcinogenic potential of aromatic amines and amides; (2) the relationship between DNA damage, measured by alkaline elution, and the formation of DNA adducts caused by aromatic amines; (3) the relationship between host cell DNA damage and bacterial mutation frequency of carcinogenic heterocyclic amines derived from pyrolysates of amino acids, meat and fish in the Salmonella/hepatocyte system; and (4)\comparison of N- and C-hyroxylations of 2-acetylaminofluorene (AAF) with debrisoquine oxidation in samples of human liver. Results so far obtained include (1) dose-dependent DNA binding and formation of individual DNA adducts Gua-C8-AAF, Gua-C8-AF and Gua-N2-AAF) were observed in rat and mouse primary hepatocytes following exposure to N-hydroxy-acetylaminofluorene (N-OH-AAF) and N-acetoxy-acetylaminofluorene (N-OAc-AAF). The patterns of DNA adducts formed in vitro for N-OH-AAF were similar to those found in vivo. A positive correlation was found between the extent of DNA strand breaks and the formation of either Gua-C8-AAF or Gua-C8-AF. (2) The data from studies of the heterocyclic amines (Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2 and IQ) indicate that cytochrome P-450-dependent N-hydroxylation of the heterocyclic amines is an obligatory step in the metabolic activation of these compounds in both subcellular and in whole cell systems; genotoxicity of these compounds quantitatively differ when measured in intact hepatocytes versus the Salmonella tester strain; and agents modulating the activity and the composition of the cytochrome P-450 system may greatly influence both toxicity and carcinogenicity of this compound in vivo. (3) The results from this study comparing the capacity of human liver microsomes of 28 individuals to metabolize debrisoquine, bufuralol, aldrin and AAF indicate that common cytochrome P-450 isoenzymes are involved in the formation of AAF metabolites while the metabolism of debrisoquine, bufuralol and aldrin is unrelated to the metabolism of this carcinogen in human liver.